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NHR-49/PPAR-α and HLH-30/TFEB cooperate for C. elegans host defense via a flavin-containing monooxygenase
- Source :
- eLife, Vol 10 (2021), eLife
- Publication Year :
- 2021
- Publisher :
- eLife Sciences Publications Ltd, 2021.
-
Abstract
- The model organism Caenorhabditis elegans mounts transcriptional defense responses against intestinal bacterial infections that elicit overlapping starvation and infection responses, the regulation of which is not well understood. Direct comparison of C. elegans that were starved or infected with Staphylococcus aureus revealed a large infection-specific transcriptional signature, which was almost completely abrogated by deletion of transcription factor hlh-30/TFEB, except for six genes including a flavin-containing monooxygenase (FMO) gene, fmo-2/FMO5. Deletion of fmo-2/FMO5 severely compromised infection survival, thus identifying the first FMO with innate immunity functions in animals. Moreover, fmo-2/FMO5 induction required the nuclear hormone receptor, NHR-49/PPAR-α, which controlled host defense cell non-autonomously. These findings reveal an infection-specific host response to S. aureus, identify HLH-30/TFEB as its main regulator, reveal FMOs as important innate immunity effectors in animals, and identify the mechanism of FMO regulation through NHR-49/PPAR-α during S. aureus infection, with implications for host defense and inflammation in higher organisms.
- Subjects :
- Staphylococcus aureus
QH301-705.5
Science
ved/biology.organism_classification_rank.species
Receptors, Cytoplasmic and Nuclear
Flavin-containing monooxygenase
Biology
General Biochemistry, Genetics and Molecular Biology
03 medical and health sciences
0302 clinical medicine
Immunology and Inflammation
transcription factors
Basic Helix-Loop-Helix Transcription Factors
Animals
PPAR alpha
Biology (General)
Model organism
Caenorhabditis elegans
Caenorhabditis elegans Proteins
Transcription factor
intestine
030304 developmental biology
0303 health sciences
Innate immune system
General Immunology and Microbiology
Effector
ved/biology
Basic Helix-Loop-Helix Leucine Zipper Transcription Factors
General Neuroscience
General Medicine
Staphylococcal Infections
biology.organism_classification
S. aureus
Immunity, Innate
3. Good health
Cell biology
Nuclear receptor
host defense
C. elegans
Oxygenases
TFEB
Medicine
Food Deprivation
030217 neurology & neurosurgery
Research Article
Subjects
Details
- Language :
- English
- Volume :
- 10
- Database :
- OpenAIRE
- Journal :
- eLife
- Accession number :
- edsair.doi.dedup.....f7957ad268709de985a3a705b8521e85